1. FIELD INVENTION
This invention relates to cross-flow filtration and more particularly to the use of charge modified organic polymeric microporous membranes for the cross-flow filtration of liquids fluids, such as biological liquids, for example plasmapheresis.
2. Prior Art
Microporous membranes are well known in the art. For example, U.S. Pat. No. 3,876,738 to Marinaccio et at (1975) describes a process for preparing a microporous membrane, for example, by quenching a solution of a film forming polymer in a nonsolvent system for the polymer. European patent application 0 005 536 (1979) and U.S. Pat. No. 4,340,479 both to Pall describe a similar process.
Other processes for producing microporous membranes are described, for example, in the following U.S. Pat. Nos:
3,642,668 to Bailey et al (1972); PA1 4,203,847 to Grandine, II (1980); PA1 4,203,848 to Grandine, II (1980); and PA1 4,247,498 to Castro (1981).
Commercially available microporous membranes, for example, made of nylon, are available from Pall Corporation, Glen Cove, New York under the trademark ULTIPOR N.sub.66. Another commercially significant membrane made of polyvinylidene fluoride is available from Millipore Corp., Bedford, Massachusetts under the trademark DURAPORE. This membrane is probably produced by the aforementioned Grandine, II patents. Such membranes are advertised as useful for the sterile filtration of pharmaceuticals, e.g. removal of microorganisms.
Various studies in recent years, in particular Wallhausser, Journal of Parenteral Drug Association, June 1979, Vol. 33 #3, pp. 156-170, and Howard et al, Journal of the Parenteral Drug Association, March-April, 1980, Volume 34, #2 pp. 94-102, have reported the phenomena of bacterial break-through in filtration media, in spite of the fact that the media had a low micrometer rating. For example, commercially available membrane filters for bacterial removal are typically rated as having an effective micrometer rating for the microreticulate membranes structure of 0.2 micrometers or less, yet such membranes typically have only a 0.357 effective micrometer rating for spherical contaminant particles, even when rated as absolute for Ps. diminuta, the conventional test for bacterial retention. Thus passage of few microorganisms through the membrane may be expected under certain conditions and within certain limits. This problem has been rendered more severe as the medical uses of filter membranes increases. Brown et al highlights this problem in CRC Critical Reviews in Environment Control, March 1980, page 279 wherein increased patient mortality and morbidity derived from contamination of sterile solutions for topical, oral, and intravenous therapy are reported.
One method of resolving this problem and its inevitable consequences, is to prepare a tighter filter, i.e. one with a sufficiently small effective pore dimension to enable the capture of the fine particulate, e.g., microorganisms, by mechanical sieving. Such filter structures, in the form of microporous membranes of 0.1 micrometer rating or less, may be readily prepared. The flow rate, however, exhibited by such structure at conventional pressure drops is low. Thus such modification of the internal geometry, i.e. pore size, of the microporous membrane is not an economical solution to the problem of bacterial breakthrough.
Attempts to increase the short life of filter media due to pore blockage and enhance flow rates through filter media having small pores have been made by charge modifying the media by various means to enhance capture potential of the filter. For example, U.S. Pat. Nos. 4,007,113 and 4,007,114 to Ostreicher, describes the use of a melamine formaldehyde cationic colloid to charge modify fibrous and particulate filter elements; U.S. Pat. No. 4,305,782, to Ostreicher et al describes the use of an inorganic cationic colloidal silica to charge modify such elements; and U.S. Ser. No. 164,797 filed June 30, 1980, now abandoned, to Ostreicher et al, describes the use of a polyamido-polyamine epichlorhydrin cationic resin to charge modify such filter elements. Similar attempts at cationic charging of filter elements were made in U.S. Pat. No. 3,242,073 (1966) and 3,352,424 (1967) to Guebert et al; and U.S. Pat. No. 4,178,438 to Hasse et al (1979).
Cationically charged membranes which are used for the filtration of anionic particulate contaminants are also known in the art. For Example charge modified filter membranes are disclosed in the Assignee's Japanese Pat. No. 923649 and French Pat. No. 7415733. As disclosed therein, an isotropic cellulose mixed ester membrane, was treated with a cationic colloidal melamine formaldehyde resin to provide charge functionality. The membrane achieved only marginal charge modification. Additionally, the membrane was discolored and embrittled by the treatment, extractables exceeded desirable limits for certain critical applications, and the membrane was not thermally sanitizable or sterilizable. Treatment of the nylon membranes prepared by the methods described in U.S. Pat. No. 2,783,894 to Lovell (1957) and U.S. Pat. No. 3,408,315 to Paine (1968) is suggested. Nylon membranes so treated also demonstrate marginal charge modification, high extractables and/or are not thermally sanitizable or sterilizable.
Assignee in order to solve the aforementioned problems has developed unique cationic charge modified microporous membranes for use in the filtration of fluids. These cationic membranes, their preparation and use are described and claimed in U.S. patent application Ser. No. 268,543, filed on May 29, 1981 in the name of Barnes et al, now U.S. Pat. No. 4,473,475 and EPC Pub. Nos. 0066 814, and U.S. patent application Ser. No. 314,307, filed on Oct. 23, 1981 in the name of Ostreicher et al, now U.S. Pat. No. 4,473,474 and EPC Pub. Nos. 0050 864.
Cationic charge modified nylon membranes covered by these inventions are now being sold by AMF CUNO Division under the trademark ZETAPOR. Pall Corp., Glen Cove, New York is also selling a cationic charge modified nylon membrane under trademark N.sub.66 POSIDYNE.
Assignees have developed an anionically charged microporous filter membrane for the removal of fine charged particulates from liquids, see copending USSN 566,764, now U.S. Pat. No. 4,604,208, entitled ANIONIC CHARGE MODIFIED MICROPOROUS MEMBRANE, PROCESS FOR CHARGE MODIFYING SAID MEMBRANE AND PROCESS FOR FILTRATION OF FLUID; however, to Applicants' knowledge, prior to this invention, no one has used such charge modified microporous filter membrane for cross-flow filtration.